In this integrated project the impact of effects of heterogeneity of responses of cells and tissues on response to hyperthermia in the clinic are explored. The goal is to arrive at diagnostic and therapeutic means to overcome the problems posed by various non-uniform heat responses. Two clinical projects examine aspects of multi-modality treatments: Radiation therapy and heat; chemotherapy and heat. In the former, the importance of scheduling of hyperthermia treatments (both number and temporal sequence) during a course of fractionated hyperthermia is tested. The latter is a randomized prospective trial in recurrent breast cancer patients of Cyclophosphamide, Adriamycin and 5 FU plus or minus hyperthermia. Two equipment development projects have as their objective the reduction of non-uniformity of heating. One deals with microwave equipment development for external applications of hyperthermia and the other with radiofrequency equipment for interstitial heating. The use of NMR, combining imaging and spectroscopy, to diagnose efficacy of hyperthermal treatment as well as mapping of bloodflow is the topic of another project. In project number six, several assays will be examined for their possible ability to predict tumor-to- tumor heterogeneity of response to heat. The final project deals with the biophysical and molecular basis of variations in heat responses, both as related to genetic heterogeneity and to induced thermotolerance.